title: Identification of potential Leptospira phosphoheptose isomerase inhibitors through virtual high-throughput screening.
abstract: The life-threatening infections caused by Leptospira serovars demand the need for designing anti-leptospirosis drugs. The present study encompasses exploring inhibitors against phosphoheptose isomerase (GmhA) of Leptospira, which is vital for lipopolysaccharide (LPS) biosynthesis and is identified as a common drug target through the subtractive genomic approach. GmhA model was built in Modeller 9v7. Structural refinement and energy minimization of the predicted model was carried out using Maestro 9.0. The refined model reliability was assessed through Procheck, ProSA, ProQ and Profile 3D. The substrate-based virtual high-throughput screening (VHTS) in Ligand. Info Meta-Database tool generated an in-house library of 354 substrate structural analogs. Furthermore, structure-based VHTS from the in-house library with different conformations of each ligand provided 14 novel competitive inhibitors. The model together with insight gained from the VHTS would be a promising starting point for developing anti-leptospirosis competitive inhibitors targeting LPS biosynthesis pathway.
authors.affiliation: SVIMS Bioinformatics Centre, SVIMS University, Tirupati 517507, India. svims.btisnet@nic.in
authors.forename: Amineni
authors.initials: A
authors.lastname: Umamaheswari
authors.forename: Dibyabhaba
authors.initials: D
authors.lastname: Pradhan
authors.forename: Marisetty
authors.initials: M
authors.lastname: Hemanthkumar
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D007919:Leptospira / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D019747:Aldose-Ketose Isomerases; C023917:phosphoheptose isomerase